Cell Reports (Jul 2021)
Metabolically controlled histone H4K5 acylation/acetylation ratio drives BRD4 genomic distribution
- Mengqing Gao,
- Jin Wang,
- Sophie Rousseaux,
- Minjia Tan,
- Lulu Pan,
- Lijun Peng,
- Sisi Wang,
- Wenqian Xu,
- Jiayi Ren,
- Yuanfang Liu,
- Martin Spinck,
- Sophie Barral,
- Tao Wang,
- Florent Chuffart,
- Ekaterina Bourova-Flin,
- Denis Puthier,
- Sandrine Curtet,
- Lisa Bargier,
- Zhongyi Cheng,
- Heinz Neumann,
- Jian Li,
- Yingming Zhao,
- Jian-Qing Mi,
- Saadi Khochbin
Affiliations
- Mengqing Gao
- Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200025 Shanghai, China; CNRS UMR 5309/INSERM U1209/Université Grenoble-Alpes/Institute for Advanced Biosciences, 38706 La Tronche, France; Pôle Franco-Chinois de Recherche en Sciences du Vivant et Génomique, 200025 Shanghai, China
- Jin Wang
- Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200025 Shanghai, China; Pôle Franco-Chinois de Recherche en Sciences du Vivant et Génomique, 200025 Shanghai, China
- Sophie Rousseaux
- CNRS UMR 5309/INSERM U1209/Université Grenoble-Alpes/Institute for Advanced Biosciences, 38706 La Tronche, France; Pôle Franco-Chinois de Recherche en Sciences du Vivant et Génomique, 200025 Shanghai, China
- Minjia Tan
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, 201203 Shanghai, China
- Lulu Pan
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, 201203 Shanghai, China
- Lijun Peng
- Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200025 Shanghai, China; Pôle Franco-Chinois de Recherche en Sciences du Vivant et Génomique, 200025 Shanghai, China
- Sisi Wang
- Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200025 Shanghai, China; Pôle Franco-Chinois de Recherche en Sciences du Vivant et Génomique, 200025 Shanghai, China
- Wenqian Xu
- Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200025 Shanghai, China; Pôle Franco-Chinois de Recherche en Sciences du Vivant et Génomique, 200025 Shanghai, China
- Jiayi Ren
- Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200025 Shanghai, China; Pôle Franco-Chinois de Recherche en Sciences du Vivant et Génomique, 200025 Shanghai, China
- Yuanfang Liu
- Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200025 Shanghai, China
- Martin Spinck
- Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany
- Sophie Barral
- CNRS UMR 5309/INSERM U1209/Université Grenoble-Alpes/Institute for Advanced Biosciences, 38706 La Tronche, France; Pôle Franco-Chinois de Recherche en Sciences du Vivant et Génomique, 200025 Shanghai, China
- Tao Wang
- CNRS UMR 5309/INSERM U1209/Université Grenoble-Alpes/Institute for Advanced Biosciences, 38706 La Tronche, France; Pôle Franco-Chinois de Recherche en Sciences du Vivant et Génomique, 200025 Shanghai, China
- Florent Chuffart
- CNRS UMR 5309/INSERM U1209/Université Grenoble-Alpes/Institute for Advanced Biosciences, 38706 La Tronche, France; Pôle Franco-Chinois de Recherche en Sciences du Vivant et Génomique, 200025 Shanghai, China
- Ekaterina Bourova-Flin
- CNRS UMR 5309/INSERM U1209/Université Grenoble-Alpes/Institute for Advanced Biosciences, 38706 La Tronche, France; Pôle Franco-Chinois de Recherche en Sciences du Vivant et Génomique, 200025 Shanghai, China
- Denis Puthier
- Aix Marseille Université, INSERM, TAGC, TGML, 13288 Marseille, France
- Sandrine Curtet
- CNRS UMR 5309/INSERM U1209/Université Grenoble-Alpes/Institute for Advanced Biosciences, 38706 La Tronche, France; Pôle Franco-Chinois de Recherche en Sciences du Vivant et Génomique, 200025 Shanghai, China
- Lisa Bargier
- Aix Marseille Université, INSERM, TAGC, TGML, 13288 Marseille, France
- Zhongyi Cheng
- Jingjie PTM Biolab (Hangzhou), 310018 Hangzhou, China
- Heinz Neumann
- Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany
- Jian Li
- Clinical Research Center, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200025 Shanghai, China
- Yingming Zhao
- Ben May Department of Cancer Research, The University of Chicago, Chicago, IL 60637, USA
- Jian-Qing Mi
- Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200025 Shanghai, China; Pôle Franco-Chinois de Recherche en Sciences du Vivant et Génomique, 200025 Shanghai, China; Corresponding author
- Saadi Khochbin
- CNRS UMR 5309/INSERM U1209/Université Grenoble-Alpes/Institute for Advanced Biosciences, 38706 La Tronche, France; Pôle Franco-Chinois de Recherche en Sciences du Vivant et Génomique, 200025 Shanghai, China; Corresponding author
- Journal volume & issue
-
Vol. 36,
no. 4
p. 109460
Abstract
Summary: In addition to acetylation, histones are modified by a series of competing longer-chain acylations. Most of these acylation marks are enriched and co-exist with acetylation on active gene regulatory elements. Their seemingly redundant functions hinder our understanding of histone acylations’ specific roles. Here, by using an acute lymphoblastic leukemia (ALL) cell model and blasts from individuals with B-precusor ALL (B-ALL), we demonstrate a role of mitochondrial activity in controlling the histone acylation/acetylation ratio, especially at histone H4 lysine 5 (H4K5). An increase in the ratio of non-acetyl acylations (crotonylation or butyrylation) over acetylation on H4K5 weakens bromodomain containing protein 4 (BRD4) bromodomain-dependent chromatin interaction and enhances BRD4 nuclear mobility and availability for binding transcription start site regions of active genes. Our data suggest that the metabolism-driven control of the histone acetylation/longer-chain acylation(s) ratio could be a common mechanism regulating the bromodomain factors’ functional genomic distribution.
